Table 1.

Therapeutic nanobodies in clinical trials.

Drug Name(s)	Format	Nanobody’s Target(s)	Indication	Current Status	Clinical Trial	Sponsor/Ref.
Caplacizumab ALX-0081 ALX-0681	Bivalent, monospecific	Von Willebrand factor-A	Acquired thrombotic thrombocytopenia purpura	FDA/EMA approved	NCT02553317 NCT02878603	Ablynx [54]
KN046	Tetravalent, bispecific, Fc-fusion protein	CTLA-4, PD-L1	Advanced solid tumors and lymphoma	Phase II/III	NCT03872791 NCT04474119 NCT04925947	Alphamab, Weill Medical College [55]
Ozoralizumab ATN-103	Trivalent, bispecific	TNFα (2), HSA	Rheumatoid arthritis	Phase II	NCT00959036 NCT01007175	Ablynx
Vobarilizumab ALX-0061	Bivalent, bispecific	IL-6R, HSA	Rheumatoid arthritis, systemic lupus erythematosus	Phase II	NCT02287922 NCT02437890	Ablynx [56]
Sonelokimab M1095	Trivalent, bispecific	IL-17F, IL-17A/F, HSA	Psoriasis	Phase II	NCT02156466 NCT03384745	Merck KGaA, Bond Avillion 2 Development LP [57]
Lulizumab BMS931699	Monomeric, pegylated	CD28	Systemic lupus erythematosus, kidney trasplantation	Phase II	NCT02265744 NCT04903054	Bristol-Myers Squibb [58]
ALX-0171	Trivalent, monospecific	RSV F-protein	RSV lower respiratory tract infection	Phase II	NCT02309320 NCT02979431	Ablynx [59]
LMN-101	Monomeric	FLaA flagellin of Campylobacter jejuni	C. jejuni infection	Phase II	NCT04182490	Lumen Bioscience
ARP1 VHH batch 203027	Monomeric	Rotavirus	Rotavirus infection	Phase II	NCT01259765	Int. Centre for Diarrhoeal Disease Research-Bangladesh [60]
Envolimab KN035	Monospecific, Fc-fusion protein	PD-L1	Advanced solid tumors, multiple primary neoplasm	Phase II	NCT03667170 NCT04182789 NCT04891198	Alphamab, 3D Medicines [61]
INBRX-109	Tetravalent, monospecific, Fc-fusion protein	Death receptor 5	Advanced solid tumors, conventional chondrosarcoma	Phase I/II	NCT03715933 NCT04950075	Inhibrx
KN044	Monospecific, Fc-fusion protein	CTLA-4	Advanced solid tumors	Phase I	NCT04126590	Intellicrown Pharm.
ALX-0141	Trivalent, bispecific	RANKL (2), HSA	Osteoporosis and bone metastasis	Phase I		Ablynx
M6495	Bivalent, bispecific	ADAMTS-5, HSA	Osteoarthritis	Phase I	NCT03583346	Merck KGaA [62]
ES101 INBRX-105	Tetravalent, bispecific, Fc-fusion protein	PD-L1, CD137	Advanced solid tumors	Phase I	NCT03809624 NCT04009460	Elpiscience, Inhibrx
ES102 INBRX-106	Hexavalent, monospecific, Fc-fusion protein	OX40	Advanced solid tumors	Phase I	NCT04198766 NCT04730843	Elpiscience, Inhibrx
BCMA nanobody CAR-T cells	Nanobody-based chimeric antigen receptor	BCMA	Relapsed/Refractory Myeloma	Phase I	NCT03664661	Henan Cancer Hospital
CD19/CD20 bispecific CAR-T cells	Nanobody-based bispecific chimeric antigen receptor	CD19/CD20	B-Cell Lymphoma	Phase I	NCT03881761	Henan Cancer Hospital
αPD1-MSLN-CAR T cells	MSLN-CAR T cells secreting anti-PD-1 nanobody	PD-1	Advanced solid tumors	Phase I	NCT04503980 NCT04489862	Shanghai Cell Therapy Group, Wuhan Union Hospital
ALX-0651	Biparatopic, monospecific	CXCR4	Multiple myeloma, non-Hodgkin’s lymphoma	Phase I terminated	NCT01374503	Ablynx
TAS266	Tetrameric	Death receptor 5	Advanced solid tumors	Phase I terminated	NCT01529307	Novartis Pharm. [51]

Abbreviations: CTLA-4, Cytotoxic T-Lymphocyte Antigen 4; PD-1, Programmed cell death 1; PD-L1, PD-1 ligand 1; TNF, tumor necrosis factor; HSA, human serum albumin; IL, interleukin; CD, cluster of differentiation; RSV, Respiratory Syncytial Virus; RANKL, ligand of receptor activator for nuclear factor-κ B; ADAMTS-5, a disintegrin and metalloproteinase with thrombospondin motifs-5; BCMA, B cell maturation antigen; MSLN, mesothelin; CXCR4, C-X-C motif chemokine receptor 4.